Research Article| Volume 78, ISSUE 6, P439-444, June 2019

Synovial C-reactive protein features high negative predictive value but is not useful as a single diagnostic parameter in suspected periprosthetic joint infection (PJI)

Published:April 16, 2019DOI:


      • Synovial fluid C-reactive protein has a high negative predictive value of 98%.
      • In periprosthetic joint infections it is significant elevated.
      • There is no additional advantage to the established MSIS criteria.



      Synovial fluid C-reactive protein (syCRP) has been recently described as a new biomarker in preoperative diagnostics to identify periprosthetic joint infections (PJI). The aim of this study was to evaluate syCRP in a large cohort of patients with suspected PJI and to calculate the optimal cut-off to diagnose PJI.


      Between September 2015 and June 2017, we prospectively included patients with suspected PJI, in which syCRP was additionally measured along with routine preoperative diagnostic serum and synovial biomarkers. We analysed the sensitivity and specificity of syCRP using receiver operating characteristic curves.


      We included 192 cases (hip n = 80, knee n = 91, shoulder n = 21) with a final diagnosis of PJI in 26 cases (14.0%). Combined for all joints, the syCRP values were significantly higher in the PJI group than in the no PJI group (median: 13.8 vs. 0 mg/l; p < 0.001). The optimal cut-off (Youden Index: 0.71) for the PJI diagnosis combined for all joints was at a syCRP value of 2.9 mg/l with a sensitivity of 88%, a specificity of 82%, and a negative predictive value of 98%.


      SyCRP features high negative predictive value but is not useful as a single diagnostic parameter in suspected periprosthetic joint infection (PJI).


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Infection
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Del Pozo JL
        • Patel R
        Clinical practice. Infection associated with prosthetic joints.
        N Engl J Med. 2009; 361: 787-794
        • Tande AJ
        • Gomez-Urena EO
        • Berbari EF
        • Osmon DR
        Management of prosthetic joint infection.
        Infect Dis Clin N Am. 2017; 31: 237-252
        • Osmon DR
        • Berbari EF
        • Berendt AR
        • Lew D
        • Zimmerli W
        • Steckelberg JM
        • et al.
        Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America.
        Clin Infect Dis Off Publ Infect Dis Soc Am. 2013; 56: e1-e25
        • Parvizi J
        • Gehrke T
        • . International Consensus Group on Periprosthetic Joint Infection
        Definition of periprosthetic joint infection.
        J Arthroplast. 2014; 29: 1331
        • Parvizi J
        • Gehrke T
        • Chen AF
        Proceedings of the international consensus on periprosthetic joint infection.
        Bone Joint J. 2013; 95-B: 1450-1452
        • Deirmengian C
        • Hallab N
        • Tarabishy A
        • Della Valle C
        • Jacobs JJ
        • Lonner J
        • et al.
        Synovial fluid biomarkers for periprosthetic infection.
        Clin Orthop Relat Res. 2010; 468: 2017-2023
        • Deirmengian C
        • Kardos K
        • Kilmartin P
        • Cameron A
        • Schiller K
        • Parvizi J
        Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?.
        Clin Orthop Relat Res. 2014; 472: 3254-3262
        • Buttaro MA
        • Martorell G
        • Quinteros M
        • Comba F
        • Zanotti G
        • Piccaluga F
        Intraoperative synovial C-reactive protein is as useful as frozen section to detect periprosthetic hip infection.
        Clin Orthop Relat Res. 2015; 473: 3876-3881
        • Omar M
        • Ettinger M
        • Reichling M
        • Petri M
        • Guenther D
        • Gehrke T
        • et al.
        Synovial C-reactive protein as a marker for chronic periprosthetic infection in total hip arthroplasty.
        Bone Joint J. 2015; 97-B: 173-176
        • Parvizi J
        • Jacovides C
        • Adeli B
        • Jung KA
        • Hozack WJ
        • Mark B
        Coventry award: synovial C-reactive protein: a prospective evaluation of a molecular marker for periprosthetic knee joint infection.
        Clin Orthop Relat Res. 2012; 470: 54-60
        • Parvizi J
        • McKenzie JC
        • Cashman JP
        Diagnosis of periprosthetic joint infection using synovial C-reactive protein.
        J Arthroplasty. 2012; 27: 12-16
        • Tetreault MW
        • Wetters NG
        • Moric M
        • Gross CE
        • Della Valle CJ
        Is synovial C-reactive protein a useful marker for periprosthetic joint infection?.
        Clin Orthop Relat Res. 2014; 472: 3997-4003
        • Vanderstappen C
        • Verhoeven N
        • Stuyck J
        • Bellemans J
        Intra-articular versus serum C-reactive protein analysis in suspected periprosthetic knee joint infection.
        Acta Orthop Belg. 2013; 79: 326-330
        • Gallo J
        • Svoboda M
        • Zapletalova J
        • Proskova J
        • Juranova J
        Serum IL-6 in combination with synovial IL-6/CRP shows excellent diagnostic power to detect hip and knee prosthetic joint infection.
        PloS One. 2018; 13e0199226
        • Ahmad SS
        • Hirschmann MT
        • Becker R
        • Shaker A
        • Ateschrang A
        • Keel MJB
        • et al.
        A meta-analysis of synovial biomarkers in periprosthetic joint infection: synovasure is less effective than the ELISA-based alpha-defensin test.
        Knee Surg Sports Traumatol Arthrosc Off J ESSKA. 2018; 26: 3039-3047
        • Lee YS
        • Koo KH
        • Kim HJ
        • Tian S
        • Kim TY
        • Maltenfort MG
        • et al.
        Synovial fluid biomarkers for the diagnosis of periprosthetic joint infection: a systematic review and meta-analysis.
        J Bone Joint Surg Am. 2017; 99: 2077-2084
        • Bossard DA
        • Ledergerber B
        • Zingg PO
        • Gerber C
        • Zinkernagel AS
        • Zbinden R
        • et al.
        Optimal length of cultivation time for isolation of propionibacterium acnes in suspected bone and joint infections is more than 7 days.
        J Clin Microbiol. 2016; 54: 3043-3049
        • Cohen J
        A power primer.
        Psychol Bull. 1992; 112: 155-159
        • Stone WZ
        • Gray CF
        • Parvataneni HK
        • Al-Rashid M
        • Vlasak RG
        • Horodyski M
        • et al.
        Clinical evaluation of synovial alpha defensin and synovial C-reactive protein in the diagnosis of periprosthetic joint infection.
        J Bone Joint Surg Am. 2018; 100: 1184-1190
        • Deirmengian CA
        • Citrano PA
        • Gulati S
        • Kazarian ER
        • Stave JW
        • Kardos KW
        The C-reactive protein may not detect infections caused by less-virulent organisms.
        J Arthroplast. 2016; 31: 152-155
        • Plate A
        • Stadler L
        • Sutter R
        • Anagnostopoulos A
        • Frustaci D
        • Zbinden R
        • et al.
        Inflammatory disorders mimicking periprosthetic joint infections may result in false positive alpha-defensin.
        Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2018; 24: 1212.e1-1212.e6
        • Zamani B
        • Jamali R
        • Ehteram H
        Synovial fluid adenosine deaminase and high-sensitivity C-reactive protein activity in differentiating monoarthritis.
        Rheumatol Int. 2012; 32: 183-188
        • Pepys MB
        • Hirschfield GM
        C-reactive protein: a critical update.
        J Clin Invest. 2003; 111: 1805-1812
        • Sproston NR
        • Ashworth JJ.
        Role of C-reactive protein at sites of inflammation and infection.
        Front Immunol. 2018; 9: 754
        • Deirmengian C
        • Kardos K
        • Kilmartin P
        • Cameron A
        • Schiller K
        • Parvizi J
        Combined measurement of synovial fluid alpha-Defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection.
        J Bone Joint Surg Am. 2014; 96: 1439-1445
        • Achermann Y
        • Sahin F
        • Schwyzer HK
        • Kolling C
        • Wust J
        • Vogt M
        Characteristics and outcome of 16 periprosthetic shoulder joint infections.
        Infection. 2013; 41: 613-620